Relationship Between Hepatic Gene Expression, Intestinal Microbiota, and Inferred Functional Metagenomic Analysis in NAFLD.

Abstract

We previously reported a lower fecal abundance of Ruminococcus spp., Faecalibacterium prausnitzii , and Coprococcus spp. in nonalcoholic fatty liver disease (NAFLD). In this article, we assess the associations between hepatic gene expression, the specific taxa, and bacterial pathways. The relationships between hepatic genes that were differentially expressed in patients with NAFLD vs healthy controls (HC) and the abundance of these specific taxa were studied. Inferred functional metagenomic analysis using Piphillin was also performed to investigate associations with bacterial pathways. Fifteen patients with NAFLD and 6 HC participated. Of 728 hepatic genes examined, 176 correlated with the abundance of Ruminococcus spp., 138 with F. prausnitzii , and 92 with Coprococcus spp. For Ruminococcus spp., genes were enriched in gene ontology (GO) terms related to apoptotic process, response to external and cytokine stimuli, and regulation of signaling. Several genes related to the Kyoto Encyclopedia of Genes and Genomes pathway insulin resistance were correlated with F. prausnitzii . The hepatic genes associated with F. prausnitzii were enriched in GO terms related to cellular response to different stimuli, apoptotic process, and regulation of metabolic pathways. For Coprococcus spp., only the GO term response to external stimulus was enriched. There was a distinct pattern of associations between hepatic genes and bacterial taxa in NAFLD vs HC. For bacterial pathways, 65 and 18 hepatic genes correlated with bacterial metabolic functions in NAFLD and HC, respectively. Hepatic gene expression related to insulin resistance, inflammation, external stimuli, and apoptosis correlated with bacterial taxa. Patients with NAFLD showed a higher presence of bacterial pathways associated with lipid metabolism.